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Gulf War and Health: Insecticides and Solvents, Volume 2
daily for 10 or 30 consecutive days or every other day for seven or 14 exposures. Cell-surface-antigen expression did not change on thymocytes, splenocytes, or bone marrow cells, but the contact-hypersensitivity response was inhibited (Punareewattana et al., 2000). The splenic macrophage-chemiluminescent response was depressed 2 and 10 days after exposure. Phagocytic ability of macrophages was not inhibited. Antibody production, as demonstrated by a plaque-forming cell assay, decreased after 10 consecutive days of exposure (Punareewattana et al., 2001).
Granulomatous changes and giant cell infiltration in the liver have been observed in rodents and dogs experiencing acute fenvalerate intoxication (Okuno et al., 1986; Parker et al., 1984). Those changes, however, are thought to reflect a foreign-body response to deposition of crystals of a type of cholesterol, 2-(4-chlorophenyl)-isovalerate ester, in the liver (Miyamoto et al., 1986). The crystals are formed by microsomal carboxylesterases, and their formation is highly specific for fenvalerate (Kaneko et al., 1986, 1988).
Long-term treatment of rats and mice with pyrethroids produced a variety of liver changes, including increased liver weights (US EPA, 1988; Hallenbeck and Cunningham-Burns, 1985; Lehman, 1965); and microgranulomatous lesions (Kaneko et al., 1986; Okuno et al., 1986; Parker et al., 1983; Ray, 1991).
Other Health Effects
Blood glucose concentrations were increased by acute pyrethroid administration to rats; type II pyrethroids were more potent than type I pyrethroids (Cremer and Seville, 1982; Ray and Cremer, 1979). Thyroid weight was increased by chronic administration of resmethrin (US EPA, 1988). In addition, behavioral changes, decreased blood glucose concentrations, decreased body weights, and increased serum urea concentrations were noted in a 90-day resmethrin inhalation experiment with rats (US EPA, 1988).
Interactions with Other Agents
Piperonyl butoxide is a microsomal mixed-function oxidase inhibitor and has been used to increase the potency of pyrethroids by decreasing their metabolism (O’Brien, 1967). Inasmuch as some of the organophosphorous insecticides inhibit esterases and pyrethroids are hydrolyzed by esterases, synergism of the actions of pyrethroids and organophosphorous insecticides might pose a hazard.
Interactions have been seen between pyrethroids and DEET. Permethrin (15, 30 or 60 mg/kg), pyridostigmine (10 mg/kg), and DEET (50, 200 or 500 mg/kg) had little or no effect on the locomotor behavior of rats when given individually (Hoy et al., 2000a). Behavioral changes were seen, however, when two of them were applied concurrently. In males, the combination of permethrin and pyridostigmine affected speed, and permethrin and DEET affected speed and thigmotaxis. No effects were seen in female rats (Hoy et al., 2000a). Hoy and colleagues (2000b) also investigated open field locomotor activity. In males pyridostigmine and DEET decreased locomotor activity, but DEET in combination with permethrin increased locomotor activity. Females treated with pyridostigmine in combination with permethrin spent more time in the center zone of the open field locomotor activity area, indicating a decrease in thigmotaxis (Hoy et al., 2000b).